Bilirubin

Bilirubin is a degradation product of haemoglobin and has a yellow-brownish colour. Bilirubin is produced 80-85% by the haemoglobin breakdown of overaged erythrocytes and 15-20% by the breakdown of other proteins containing haem; under pathological conditions also in cases of maturation disorders of the erythrocytes in the bone marrow (ineffective erythropoiesis).

In the serum bilirubin is found either as:

• Indirect, also called non-conjugated bilirubin, which is attached to albumin because of its poor water solubility

or as

• direct, also called conjugated bilirubin covalently esterified with glucuronic acid (glucuronidation) (bilirubin monoglucuronide)

before. Delta Bilirubin is a fraction of glucuronidated bilirubin covalently bound to albumin (below the detection limit in healthy individuals).

The measurement of direct (glucuronidated) bilirubin is detected:

• bilirubin monoglucuronide,
• bilirubindiglucuronide and
• Delta bilirubin.

Delta-Bilirubin has a long half-life (about 20 days) due to the albumin binding proteins. In the case of cholestatic diseases, delta bilirubin can account for up to 50 - 90 % of the total bilirubin!

Standard values:

Total (in serum and plasma): 0.2 to 1.1 mg/dl or up to 19 µmol/lDirect
bilirubin (in serum and plasma): 0.05 to 0.3 mg/dl or up to 5 µmol/lIndirect
bilirubin (in serum and plasma): < 0.8 mg/dl

According to the recommendations for classification and graduation of toxicities, bilirubinemia is graduated as follows:

• Grade 0: <1.25 mg/dl
• Grade 1: 1.25-2.5mg/dl
• Grade 2:2.6-5mg/dl
• Grade 3:5.1-10mg/dl
• Grade 4: >10mg/dl

Pathologically elevated bilirubin is found in:

viral hepatitis, (primarily biliary) liver cirrhosis, hepatocellular carcinoma and metastases, drug icterus, fatty liver cholestasis, hypoxic hepatopathy, right heart failure, liver congestion, congenital secretion disorder, Pregnant swollen, occlusive cholangitis, cholangitis, idiopathic recurrent cholestasis, Meulengracht's disease, polycythemia, shunt hyperbilirubinemia, increased blood loss, hemolytic anemia and toxic hemolysis.

1. Sticova E et al (2013) New insights in bilirubin metabolism and its clinical implications,World J Gastroenterol 19:6398-6407
2. Erlinger S et al (2014) Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences: Gastroenterology 146:1625-1638.